NAMRU-D attends

54th Society of

Toxicology

1

NAMRU-D Continues to

Investigate Chemical

Exposure

2

NAMRU-D attends

Shoresh Working Group

Meeting

2

NAMRU-D Investigates

Hypoxia Mitigation 3

NAMRU-D’s Past

Quarter Visitors 4

CO’s Corner 5

NAMRU-D is Navy Medicine’s world class, global aeromedical and toxicology research leader. Our efforts and innovative products are aligned with operational requirements to solve the naval and joint warfighter challenges of the future.

VISION

To maximize warfighter performance and survivability through premier aeromedical and environmental health research- delivering solutions to the field, the Fleet, and for the future.

MISSION

INSIDE THIS

ISSUE

Spring Volume 5, Issue II

Science Update

Naval Medical Research Unit Dayton Wright-Patterson AFB, Ohio

By: Dr. Lisa Sweeney

S cientists from Naval Medical Research Unit

Dayton’s (NAMRU-D) Environmental

Health Effects Directorate attended and

presented research during the 54th Annual Meet-

ing of the Society of Toxicology (SOT) held in San

Diego, CA March 22 to 26, 2015. This meeting

brings together approximately 6,900 toxicologists

from over 50 countries to discuss recent advanc-

es and technologies in toxicological research. Dr.

Karen Mumy, Dr. Lisa Sweeney, LCDR Jennifer

Mueller and LCDR Carlis Brown attended from

NAMRU-D. Dr. Sweeney chaired a platform ses-

sion on applications of ToxCast/Tox21 data. Dr.

Sweeney and Dr. Mumy were authors or co-

authors on two poster presentations, both of

which described efforts done in conjunction with

Department of Defense partners.

NAMRU-D scientists teamed up with 711th Hu-

man Performance Wing/RHDJ U.S. Air Force sci-

entists for an evaluation of the potential effects of

“Alcohol-to-Jet” (ATJ) alternative jet fuels. The

authors determined that the appropriate occupa-

tional exposure limits for these fuels are equiva-

lent to those for traditional Air Force jet fuel

(that is, JP-8). Dr. Mumy and Dr. Sweeney of

NAMRU-D were co-authors of this work which

was presented during a poster session entitled,

“Toxicity of Chemical Mixtures.”

In collaboration with U.S. Army, Dr. Sweeney

presented a poster entitled, “Development of a

toxicokinetic model for the insensitive munitions

(IMX) component 2,4-dinitroanisole (DNAN),” in

a session focused on Biological Modeling. IMX

formulations are less susceptible to unintentional

detonation than conventional munitions, but their

potential hazard to humans is unknown. Scientists

at NAMRU-D conducted laboratory studies to

evaluate the absorption, distribution, metabolism,

and elimination of DNAN and its more toxic me-

tabolite2,4-dinitrophenol (DNP) in rats. These

data and similar data generated by the Army for

nonhuman primates (rhesus macaques) were used

by Dr. Sweeney to develop preliminary physiologi-

cally based pharmacokinetic (PBPK) models of

DNAN and DNP in rats, macaques, and (by ex-

trapolation) humans. The PBPK model was used

to generate estimated human no-effect exposure

levels for DNAN based on no-observed adverse

effect levels determined in laboratory animals.

The human no-effect levels may be used to guide

the selection of occupational and environmental

exposure limits for DNAN.

NAMRU-D Presents at the

54th Annual Meeting of the Society of Toxicology:

Alternative Jet Fuel and Insensitive Munitions Research

Dr. Lisa Sweeney presented

her research on the

Development of a

Toxicokinetic Model for

Insensitive Munitions (IMX)

Component 2, 4-

Dinitroanisole at the 2015

Society of Toxicology (SOT)

held March 22 - 26 in San

Diego, CA. Dr. Sweeney is a

Senior PBPK Toxicologist at

NAMRU-D and has attended

the annual SOT meeting

since 1995.

Page 2 Science Update

Investigating Chemical Exposure

at High Altitudes in High Performance Aircraft By: LCDR Carlis Brown & Dr. Deirdre Mahle (U.S. Air Force 711 HPW/RHDJ)

The USAF has been identifying potential contributing factors to epi-

sodes of suspect hypoxia seen in pilots during training missions. In-

flight emergencies with high performance aircraft indicate a gap in our

knowledge or understanding of stressors in the environment and

impact on physiology and/or toxicology. The 711th Human Perfor-

mance Wing (HPW), Molecular Bioeffects Branch has teamed with

NAMRU-D to further investigate identified data gaps for chemical

exposure at high altitudes. One of the uncertainties is the effects of

volatile organic chemicals (VOCs) that have been detected as a cock-

pit contaminant, of which toluene is one example. Toluene is a

chemical with a good scientific exposure database that can easily be

measured in blood and tissues and it has a known physiologically

based pharmacokinetic (PBPK) model for the human exposure as well

as a corollary PBPK model for a rat. In addition, toluene has been

shown to have a link to hypoxia in some studies which increases its

relevance to this study. NAMRU-D was asked to develop a system

that could simulate the inhalation exposure of toluene at high alti-

tudes in an animal model. Such a system would duplicate conditions

experienced in flight and allow the AF to determine whether or not

changes in altitude will significantly increase the uptake of VOCs

compared to exposures at normal ambient atmospheres.

NAMRU-D Attends 2015 Shoresh Working Group Meeting in Israel

Left to right: Dr. Deidre Mahle, Mr. Richard James, and LCDR Carlis Brown

have been collaborating to investigate chemical exposure at high altitudes in high performance aircraft.

By: CDR Michael Lowe

O n March 13-21, 2015 members of Naval Medical Research

Unit Dayton’s (NAMRU-D) Aeromedical scientific research

staff attended and presented at the Shoresh Working

Group Meeting in Ramat Gan, Israel as invited members of the U.S.

Department of Defense/Israeli Defense Forces Aeromedical

Working Group. CDR Michael Lowe, Head, Biomedical Science

Department, NAMRU-D and Dr. Michael Reddix, Senior Research

Psychologist at NAMRU-D, presented three of the four NAMRU-D

briefs during the 17th Shoresh meeting. Dr. Richard Arnold,

Aeromedical Research Director, NAMRU-D phoned in to the

meeting to present NAMRU-D’s command overview. This is the

first Shoresh meeting to include the U.S. Air Force and U.S. Navy

and also the first to look at aeromedical research priorities.

Various topics and issues regarding challenges of operating in the

extreme aerospace environment were discussed. Dr. Reddix

covered Simulation of Aviation Illusions and Advanced

Computerized Color Vision Screening. NAMRU-D’s hypoxia

research, specifically exposure sequel, recovery and mask based

sensors was presented my CDR Lowe. The hypoxia brief included

accomplishments with initial collaborations in foreign comparative

testing featuring the Israeli company Elbit. This work presents a

solid starting point for future collaborations in hypoxia and other

aeromedical domains is the current the U.S. and Israel joint effort

investigation on mask sensors in hypoxia.

NAMRU-D’s fatigue laboratory, Disorientation Research Device,

various cognitive tests, EEG capabilities, and other physiological

measures provide

considerations for future

jointness. In fact, at the

end of the meeting the

Aeromedical topics for

possible collaboration and

inclusion in the final

working group document

for action items were

produced, prioritized, and

presented to the Surgeon

Generals on the last day.

Three NAMRU-D centric

topics made the list of 11

items of which CDR Lowe is the NAMRU-D point of contact for

each. These focal areas were: 1) Spatial Disorientation, 2) Hypoxia,

and 3) Fatigue.

As a result of the meeting the foundation is being laid through

mutually beneficial information exchanges and potential research collaborations with no expectation for funding exchanges. .

NAMRU-D’s attendance at the working group symbolized the first

step in forming a collaborative relationship with Aeromedical

entities in Israel and significantly builds upon the foundations of the

prior joint work on hypoxia sensors with Elbit. CDR Lowe strongly

recommended that NAMRU-D attend the next Shoresh Working

Group and further commits to this working group fully in the

future with an even larger contingent.

CDR Lowe and Dr. Reddix at a

function during the 2015 Shoresh Working Group Meeting .

Page 3 Science Update

NAMRU-D Continues to Investigate Hypoxia Mitigation

By: Dr. Jeffrey Phillips

N aval Medical Research Unit

Dayton’s hypoxia laboratory

focuses both on quantifying

the performance effects of hypoxia

and identifying emerging technologies

to provide fail-safe hypoxia

mitigation. The hypoxia lab is staffed

with experimental psychologists,

physiologists, and biomedical

engineers. NAMRU-D Investigators

have executed numerous studies

evaluating off-the-shelf biomedical

sensors for their ability to reliably

detect an impending hypoxic threat

before the operator experiences

significant performance degradation.

Technologies evaluated include near

infrared spectroscopy, pulse

oximetry, reflectance pulse

oximetry, eye tracking, and

pupilometry.

Both the Air Force and Navy are

currently developing in-mask gas

sensor suites to provide warnings to

aviators when a life support malfunction

occurs. Unfortunately, most

commercial gas sensors do not perform

well in tactical aviation environments

due to the large variations in barometric

pressure, humidity, and temperature.

NAMRU-D houses a state-of-the-art gas sensor testing facility which allows gas

and chemical sensors to be evaluated in

conditions equivalent to the flight

environment. Sensors are tested in a

hypobaric chamber while pressure,

humidity and temperature are

manipulated. To date, twenty-two

sensors have been evaluated in our

facility. This testing has verified that

sensor sensitivity and specificity

improvements are still required before

they can reliably provide significant

hypoxia mitigation in-flight.

The NAMRU-D hypoxia team has also

conducted multiple studies to model the

onset of hypoxia performance effects as

well as the recovery of performance

following hypoxia exposure. Breaking

with traditional teaching, NAMRU-D

study results suggest that operators

exposed to hypoxic environments experience significant

performance degradation at a much earlier time point than

predicted by the Time of Useful Consciousness Tables customarily

used for risk assessments. Furthermore, previously unappreciated

subtle performance effects have been

found to persist for hours following

exposure. The most recent study

also found empirical evidence of an

oxygen paradox as subjects

experienced the largest performance

deficits while they were being administered a five minute treatment

with 100% oxygen following hypoxia

exposure. This implies that following

hypoxia exposure, operators could

remain significantly impaired

throughout the remainder of the

flight.

In the coming years, the NAMRU-D

hypoxia lab will continue to conduct

experiments to better understand the

performance effects of hypoxia, to

test hypoxia-mitigation sensors for

their ability to perform in the tactical

flight environment, and to identify a

hypoxia recovery gas mixture that will

provide quick recovery from hypoxia

exposure without further

compromising performance.

Small Hypobaric Environmental Chamber for sensor testing in aviation-relevant environmental conditions.

The chamber can vary pressure, temperature, humidity, & airflow on sensors of interest.

Dr. Jeffrey Phillips (back right) explains to CAPT Burghardt, PMA-202 (back left) NAMRU-D’s

capabilities to further investigate hypoxia mitigation during the CAPT’s visit on 19 March, 2015.

Page 4 Science Update

Becker, W.J., Geyer, D.J., Gomez, K., & Littman, E.M. (2015, May). Pharmacokinetics and Efficacy of Intranasal Scopolamine Spray. Poster presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Bradley, J.L., Reddix, M.D., Folga, R.V., & Tapia, M.L. (2015, May). Laser-Pointer Illumination Events in Naval Aviation Operations. Presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Caldwell, J.A. & Caldwell, J.L. (2015, May). Understanding and managing fatigue in aviation. Workshop at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Caldwell, J.L. (2015, May). The evidence base for use of modafinil to mitigate fatigue. Workshop at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Caldwell, J.L. (2015, May). Aviation Fatigue Countermeasures Pat II: Advances in Fatigue Management. Workshop at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Drummond, L.A., Funke, M.G., Phillips, J.B., Robinson, F.E., Warner, S.W., Geyer, D.J., & Gomez, J. (May, 2015). Recovery from Hypoxic Exposure. Presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Funke, M.G., Gomez, J., Phillips, J.B., Lee, M.C., Wright, & Becker, W.J. (2015, May). Performance Costs Associated with Modifications to the Oxygen Delivery Schedule of the On-

Board Oxygen Generating System. Poster presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida. Gao, H., Reddix, M.D., & Kirkendall, C. (2015, May). Can Operationally-relevant accuracy and reaction-time metrics guide the development of color-vision standards?. Presentation at

85th Annual Aerospace Medicine Association Conference, Orlando, Florida. Hartzler, B.M. (March, 2015). Predicting performance during chronic sleep loss: Identification of factors sensitive to individual fatigue resistance. Technical Report retrieved

from Defense Technical Information Center.

Hartzler, B. M., Chandler, J.F., & Levin, C.B.S. (2015, May). Identification of measures and moderators to improve prediction of impairments due to chronic sleep loss. Poster

presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Littman, E.M., Lawson, B., Brill, J.C., & Rupert, A. (May, 2015). Near-Future Technological Countermeasures for Spatial Disorientation in Flight. Presentation at International Symposium on Aviation Psychology.

McGowan, K.J., Gao, H., & Whitwell, K.J. (May, 2015). United States Naval Aerospace Optometry. Presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

Patterson, F.R., Williams, H.P., Arnold, R.D, & Folga, R.V. (May, 2015). Aviator Black Hole Illusion: Validation Training Countermeasures for Newly Identified Causal Factors.

Presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida. Phillips, J.B., Robinson, F.E., Drummond, L. A., & Funke, M.G. (May, 2015). Time of Useful Performance: A Complement to the Time of Useful Consciousness Table. Presentation at

85th Annual Aerospace Medicine Association Conference, Orlando, Florida. Phillips, J.B., Grigsby, C., Mayes, R., & Tripp, L. (May, 2015). In-Flight Hypoxia: From Sensors to Biomarkers. Presentation at 85th Annual Aerospace Medicine Association

Conference, Orlando, Florida. Sweeney, L.M., Sommerville, D.R., Channel, S.R., Sharits, B.C., Gargas, N.M., and Gut, C.P., Jr. (2015). Evaluating the validity and applicable domain of the toxic load model:

impact of concentration vs. time profile on inhalation lethality of hydrogen cyanide. Regul. Toxicol. Pharmacol. 71:571-584.

Williams, H.P., Littman, E.M., Folga, R.V., & Patterson, F.R. (May, 2015). Field of view evaluation for flight simulators used in spatial disorientation training. Presentation at 85th Annual Aerospace Medicine Association Conference, Orlando, Florida.

NAMRU-D Products & Presentations

03.19.2015. CAPT Andrews, NAMRU-D Commanding Officer (left) introduced

Brigadier General Payne, AFMOA (right) to NAMRU-D’s Disorientation Research Device. CDR Folga (2nd on right) briefed the devices capabilities. Brigadier

General Timothy Jex, 711 Human Performance Wing Commander (center) accompanied Brigadier General Payne’s tour.

NAMRU-D’s Visitors

03.19.2015. Dr. Jeffrey Phillips demonstrates the functions of the head mounted sensors connected to an

Reduced Oxygen Breath Device to CAPT Burghardt, PMA-202 during a visit to the NAMRU-D facilities.

04.23.2015. NAMRU-D hosted a

visit from Environmental Tectonics Corporation (ETC) Board of

Directors to observe a motion demonstration of NAMRU-D's

Disorientation Research Device. Left to right: CAPT Lee, XO; H. F.

"Gerry" Lenfest, Chairman of the Board of Directors; CAPT Andrews,

CO; Robert L. Laurent, Jr., Chief Executive Officer and President;

CDR Folga; and Winston E. Scott, Director. Right to left: Linda J. Brent;

Director and Roger Colley, Director.

04.23.2015. CDR Folga highlights the Disorientation Research Device’s future

applications for the safety of the war fighter to Environmental Tectonics Corporation ETC Board of Directors.

Science Update Page 7

It is now just past Memorial Day as I write this spring edition and the opportune time to reflect

on our fallen warriors and their ultimate sacrifice. Our mission is all about them. Let their

death be not in vain, but a spark to ignite motivation to make the future better and safer for

those in harms way. All 75 personnel at NAMRU-D know their unique mission, but even more

importantly there is a collective understanding and selfless commitment that we exist for the

joint warfighter. All of our science and efforts are aligned with operational requirements and

our products can and do make a difference in the performance and survivability of those on the

battlefield. Even basic Research & Development (R&D) can be the foundation for a future

cutting edge solution in any operational setting.

Despite the obstacles of bureaucracy, over-regulation, and limited/uncertain funding, successful

R&D starts with an idea. At NAMRU-D, our scientists have ideas that are based on fleet

experience and operational input. That idea needs to be fueled not only by passion and

persistence, but will have to grow and ideally be put to use in an operational setting and applied

by the warfighter. It is during this growth phase that our scientists sprinkle on some intellect,

creativity, teamwork, jointness, collaboration, and yes a touch of luck to finish the main course

and satisfy the appetite of our eaters in the fleet.

This Science Update covers only a 3 month snapshot of life at NAMRU-D and showcases some of our toxicological and

aeromedical accomplishments, international involvement with Israel, and the constant, high visible tours of VIPs and high

ranking officials and agencies. What is not covered is the mindset, motivation, and professionalism of the NAMRU-D team

that make the R&D into a way of life with the pursuit of that product or system that will ultimately reach the warfighter and

maybe someday save lives. I salute those who died for our freedom and commend those who commit their lives to R&D in

support of our heroes. NAMRU-D stands ready for ideas, sound science, and continued growth of capabilities to support

our nation’s finest.

Commanding Officer’s Corner

Captain Jeffrey M. Andrews,

MSC, USN

Commanding Officer

Naval Medical Research Unit Dayton

Wright-Patterson Air Force Base

2624 Q Street, Building 851, Area B

WPAFB, OH 45433-7955

Phone: 937-938-3872

Fax: 937-904-8814

www.med.navy.mil/sites/nmrc/Pages/namrud

Commanding Officer

CAPT Jeffrey Andrews, MSC, USN

Executive Officer

CAPT Rees L. Lee, MC, USN

Naval Medical Research Unit Dayton is on Facebook!

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Aeromedical & Environmental Health Research